GI (P00074) Protein Card

General Information

Name	GI
Organism	Conus geographus (Geography cone)
Organism region	Indo-Pacific
Organism diet	piscivorous
Protein Type	Wild type
Protein precursor	GI precursor (2975) GI precursor (5714)
Notes	Paralysis in vertebrates. This is the very first caracterised toxin from a Conus venom (Gray et al. 1981).

Classification

Conopeptide class	conotoxin
Gene superfamily	A superfamily
Cysteine framework	I
Pharmacological family	alpha conotoxin

Sequence

ECCNPACGRHYSC(nh2)

Modified residues

position	symbol	name
14	nh2	C-term amidation

Sequence evidence

protein level

Average Mass

1437.59

Monoisotopic Mass

1436.48

Isoelectric Point

8.31

Extinction Coefficient [280nm]

1490.00

Activity

IC50: Nicotinic acetylcholine receptors

Target	Organism		IC50		n_hill	Agonist	Ref
α1β1γδ	M. musculus	(site 2)	60uM			10nM [125I]-R-Bgtx	Groebe,D.R. et al. (1997)
		(site 1)	1.3nM	+/-0.3		10nM [125I]-R-Bgtx	Groebe,D.R. et al. (1997)
			20nM			500nM Ach	Johnson,D.S. et al. (1995)
		(site 2)	5.86 nM	[5.01-6.86]	1.24	ACh (10 uM)	Ning,J. et al. (2018)
	T. marmorata	(site 2)	87nM	+/-24		10nM [125I]-R-Bgtx	Groebe,D.R. et al. (1997)
		(site 1)	4.5nM	+/-1.3		10nM [125I]-R-Bgtx	Groebe,D.R. et al. (1997)
α2β2	R. norvegicus		>5uM			300uM Ach	Johnson,D.S. et al. (1995)
α2β4	R. norvegicus		>5uM			300uM Ach	Johnson,D.S. et al. (1995)
α3β2	R. norvegicus		>5uM			300uM Ach	Johnson,D.S. et al. (1995)
α3β4	R. norvegicus		>5uM			300uM Ach	Johnson,D.S. et al. (1995)
α4β2	R. norvegicus		>5uM			300uM Ach	Johnson,D.S. et al. (1995)
α4β4	R. norvegicus		>5uM			300uM Ach	Johnson,D.S. et al. (1995)
α7	R. norvegicus		>5uM			500uM Ach	Johnson,D.S. et al. (1995)
α9	R. norvegicus		>5uM			100uM Ach	Johnson,D.S. et al. (1995)
α9α10	R. norvegicus		9.35 uM	[7.02-12.5]		ACh (10 uM)	Ning,J. et al. (2018)

Synthetic variants

GI [N4>Benzoylphenylalanine]	ECC(Pbf)PACGRHYSC
GI [R9A]	ECCNPACGAHYSC(nh2)
GI [S12>Benzoylphenylalanine]	ECCNPACGRHY(Pbf)C
GI antitoxic analog	CANPACGRHYS(nh2)
GI[E1A]	ACCNPACGRHYSC(nh2)
GI[G8A]	ECCNPACARHYSC(nh2)
GI[H10A]	ECCNPACGRAYSC(nh2)
GI[N4A]	ECCAPACGRHYSC(nh2)
GI[P5A]	ECCNAACGRHYSC(nh2)
GI[R9A]	ECCNPACGAHYSC(nh2)
GI[S12A]	ECCNPACGRHYAC(nh2)
GI[Y11A]	ECCNPACGRHASC(nh2)

References

Gray,W.R., Luque,A., Olivera,B.M., Barrett,J. and Cruz,L.J. (1981) Peptide toxins from Conus geographus venom J. Biol. Chem. 256:4734-4740

Groebe,D.R., Gray,W.R., and Abramson,S.N. (1997) Determinants involved in the affinity of alpha-conotoxins GI and SI for the muscle subtype of nicotinic acetylcholine receptors Biochemistry 36:6469-6474

Guddat,L.W., Martin,J.A., Shan,L., Edmundson,A.B. and Gray,W.R. (1996) Three-dimensional structure of the alpha-conotoxin GI at 1.2 A resolution Biochemistry 35:11329-11335

Pardi,A., Galdes,A., Florance,J. and Maniconte,D. (1989) Solution structures of alpha-conotoxin G1 determined by two-dimensional NMR spectroscopy Biochemistry 28:5494-5501

Gehrmann,J., Alewood,P.F. and Craik,D.J. (1998) Structure determination of the three disulfide bond isomers of alpha-conotoxin GI: a model for the role of disulfide bonds in structural stability J. Mol. Biol. 278:401-415

Johnson,D.S., Martinez,J., Elgoyhen,A.B., Heinemann,S.F. and McIntosh,J.M. (1995) alpha-Conotoxin ImI exhibits subtype-specific nicotinic acetylcholine receptor blockade: preferential inhibition of homomeric alpha 7 and alpha 9 receptors Mol. Pharmacol. 48:194-199

Ning,J., Li,R., Ren,J., Zhangsun,D., Zhu,X., Wu,Y. and Luo,S. (2018) Alanine-Scanning Mutagenesis of α-Conotoxin GI Reveals the Residues Crucial for Activity at the Muscle Acetylcholine Receptor Mar Drugs 16:507

Internal links

Protein Precursor	GI precursor (2975) GI precursor (5714)
Nucleic acids
Structure	THE 1.2 ANGSTROM STRUCTURE OF G1 ALPHA CONOTOXIN ALPHA CONOTOXIN GI: 2-3;7-13 DISULFIDE BOND ISOMER, NMR, 25 STRUCTURES ALPHA CONOTOXIN GI: 2-7;3-13 (NATIVE) DISULFIDE BOND ISOMER, NMR, 35 STRUCTURES ALPHA CONOTOXIN GI: 2-13;3-7 DISULFIDE BOND ISOMER NMR, 24 STRUCTURES

External links

UniProtKB/Swiss-Prot	P01519
Ncbi	1NOT_A, 1XGA_A, 1XGB_A, 1XGC_A

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